pain

1. Adequate therapy for chronic non-cancer
1
pain:
Current barriers and thoughts for
the future
Dr. Yoram Shir
Alan Edwards Pain Management Unit
McGill University Health Centre

2. 2
Disclosure
The speaker cannot identify any potential conflict of
interest and has no relationships that should be
disclosed

3. Objectives
 To review the prevalence of chronic non-cancer
pain (CNCP)
 To review specific therapeutic approaches
 To recognize the barriers for better treatment
 To suggest changes in our approach to CNCP

4. 4
Pain
“An unpleasant sensory and emotional
experience associated with actual or potential
tissue damage or described in terms of such
damage” (IASP)

5. 5
The gate control theory

6. 6
Brain
Peripheral
nociceptors
Pain pathways
Spinal cord

7. 7
Types of pain
 Acute vs. chronic
 Malignant vs. benign
 Physiological vs. pathological
 Nociceptive vs. visceral
 Neuropathic
 Idiopathic

8. 8
Acute vs. Chronic Pain
Acute
 Symptom
 Short-term
 Warning sign
 Anxiety
 Responds well
 Single treatment
Chronic
 Disease
 Long-term
 False alarm
 Depression
 Less likely to respond
 Multidisciplinary approach

9. 9
Non malignant vs. malignant pain
”…we have deliberately not used the term ‘non-malignant
pain’ because unrelieved chronic pain
associated with any disease is indeed malignant”
(Gourlay et al, 1991)

10. Definition: chronic non-cancer pain
10
“…pain that has been present for at least six
months or that has persisted longer than the
expected time for tissue healing or resolution of
the underlying disease process.” [Canadian Pain Society
Guidelines, 2002]

11. 11
Prevalence of chronic pain
 > 80% of cancer patients
 10-40% of the general population
 > 50% following some surgeries
 ~ 25% in hospitalized populations
 45-80% of the elderly populations
 25% in Canada

12. Pain in the elderly
 In the USA, 17% of the population is 60 years
or older
 More than 38 million individuals in the USA
are 65 years or older
 By 2030 the number of persons aged 65 years
or older in the USA will increase to an
estimated 71 million
 By 2025, 1.2 billion people worldwide will be
aged 60 years or older

13. Prevalence of chronic pain in
elderly people
 Difference between community dwelling
people & long term care
 Prevalence 3.7%-80%
 80% of old people with cancer
 Could be due to central degenerative changes,
muscle weakness & slower rate of tissue
healing

14. 14
Burden of chronic pain
 Became a global disease
 Worldwide crisis
 In the USA alone:
 Half million lost workdays/annum
 Healthcare costs > $150 billion/annum
 Steady increase in cost (e.g., 70% 1988-1995)

15. 15
Chronic pain in Canada
 2/3 of Canadian primary care practitioners
believe that moderate/severe chronic pain is
not well managed
 Median waiting time for 1st appointment in
multi-disciplinary pain centers in Canada is 6
months (2-14 months)

16. 16
The chronic pain spiral
PPaaiinn
CCeenntteerreedd
LLiiffee
INJURY
ILLNESS
TISSUE DAMAGE
PERSISTING PAIN
LIMITS ACTIVITIES
WEAK TIGHT
MUSCLES
DECONDITIONING
HURT VS. HARM
SURGERY
STIGMA
LOSS OF CONTROL
DECREASED PHYSICAL
& SOCIAL
FUNCTIONING
DEPRESSION
Jovey RD. Pain focus. 2007;1.

17. 17
Pain assessment tools
 Pain measurement
 Pain History
 Psychosocial history (mood, substance abuse,
functional level, family, occupation, etc.)
 Goals & expectations

18. Interpreting changes in pain intensity
18
Decrease in pain
intensity
Clinical significance
10 – 20 % Minimal
≥ 30% Moderate
≥ 50% Substantial

19. Barriers to effective pain management
The physician:
 Believing patients always tell when having pain
 Lack of training/knowledge
 Fear of regulatory scrutiny
 Concerns about addiction and side effects
 Time consuming
 Pain management is secondary to disease management
 Believing pain is a symptom, not a disease
 Failure to define goals and expectations
19

20. 20
Goals
PALLIATION REHABILITATION
SIDE EFFECTS
COST
AVAILABILITY
CLINICAL EXPERTISE

21. Optimize balance between
analgesia and adverse effects
ANALGESIA ADVERSE EFFECTS

22. Barriers to effective pain management
The patient:
22
 Misconception that pain is normal
 Unwillingness to report pain
 Fear of side effects and addiction
 Believing that therapy may prevent control of
more severe pain in the future
 Cognitive impairment in elderly
 Depression
 Passive coping strategies

23. Barriers to effective pain management
The system:
 Lack of resources
 Wrongful use/investments of the existing limited
resources
 Lack of basic education
 Permissive compensatory system
23

24. The reality of CNCP
 Once developed, our ability to effectively treat
CNCP is restricted
 Nevertheless, most traditional basic research efforts
& clinical pain-relieving approaches focus on pain
palliation rather than prevention

25. Palliative therapeutic modalities
• Non-pharmacological approaches
• Analgesic medications
• Invasive interventions

26. 26
WHO analgesic ladder
I II
III
Pain Intensity
non-opioids
+ adjuvants
weak-opioids
+ non-opioids
+ adjuvants
strong-opioids
non-opioids+
+ adjuvants

27. 27
Analgesic ladder:
multimodal modification
I II III
Pain Intensity
non-opioids
non-invasive+
measures
opioids
non-invasive+
simple invasive +
measures
opioids
non-invasive+
super invasive +
measures

28. 28
Non-pharmacological measures
 Psychological & behavioral therapy
 CAM & diet
 Relaxation, biofeedback, hypnosis
 Physical modalities

29. 29
Invasive measures
 Trigger point injections
 Nerve blocks
 IV lidocaine/ketamin/bisphosphenates infusions
 Spinal axis interventions
 Sympathectomy

30. 30
Super -invasive measures
 Peripheral nerve, spinal cord & brain stimulation
 Implanted spinal pump
 Ablative surgery

31. 31
Pharmacological modalities
 Non-opioid analgesics
 Opioids
 Adjuvants
 Marijuana and marijuana derivates

32. 32
Non-opioid analgesics – tramadol
 Centrally acting synthetic non-opioid structurally related
to codeine
 Tramadol/morphine potency ratio: 1:4
 2 enantiomers:
 (-) Tramadol – weak mu agonist
 (+) Tramadol - inhibits serotonin reuptake
 Up to 95% oral bioavailability

33. 33
Dose recommendation
 Tramadol/acetaminophen: 1-2 Tb. Every 4-6h
 Tramadol extended release: once daily, not
beyond 400mg
 Reduced dose in kidney disease

34. 34
Clinical aspects
 Effective in nociceptive, neuropathic & mixed pain
conditions
 Abuse potential:
 Probably less than opioids
 Similar to NSAID
 Side effects:
 Serotonin syndrome
 Similar to opioids: dizziness, nausea, vomiting,
sweating
 < opioids: constipation, sedation

35. 35
Nucynta
 Centrally acting analgesic
 Dual action: μ-opioid agonist & NA reuptake
inhibitor.
 Potency between tramadol and morphine in
effectiveness
 Immediate and extended -release preparations
 50mg Tb., up to 250mg/daily

36. 36
Adjuvant analgesics
 Mood stabilizers & antidepressants
 Sleep promoters
 Anti - epileptics
 Marijuana derivates
 Steroids

37. 37
Antidepressants:
Tricyclics - amitriptyline
Suggested mechanism:
 CA reuptake inhibitors
 Affinity for opioid receptors
 NMDS blockers
 Voltage-gated Na(+) channels blockers

38. 38
Amitriptyline
 Clinically effective in:
 Postherpetic neuralgia
 Diabetic neuropathy
 Tension type headache
 Central pain due to stroke
 Fibromyalgia
 Common anti-cholinergic side effects
 Suggested dose: 10 (5) – 75mg

39. 39
Noradrenergic/serotonergic
antidepressant
 Could possess direct analgesic properties:
 Mirtazapine (remoron) - tension-type headache
 Bupropion (welbutrin) - neuropathic pain
 Venlafaxine (effexor) – Visceral & neuropathic pain
 Duloxetine (cymbalta) – diabetic peripheral
neuropathy, fibromyalgia , non-radicular LBP

40. 40
Anticonvulsants
 Commonly used in chronic pain
 Possible analgesic mechanisms:
 increasing GABA inhibition
 modulating sodium and calcium channels
 inhibiting excitatory amino acids
 decreasing abnormal neuronal hyperexcitability

41. 41
Carbamazepine
 Traditionally regarded as the gold-standard
 Effective in trigeminal neuralgia & diabetic neuropathy
 Side effect profile opened the way for gabapentin
 No clinical studies comparing it to gabapentin &
pregabalin

42. 42
Gabapentin
 Acts through increased synaptic GABA
& calcium blockade at the CNS
 Proven effects:
 Post traumatic neuropathic pain
 Peripheral neuropathy
 PHN
 Preemptive analgesia for PO pain
 Neuropathic pain due to cancer

43. 43
Gabapentin – in what dose?
 Effective dose: 900-1,800mg/day
 Dose range seen at the clinic: 100-9,600mg/day
 Suggested dose:
 Start with 100mg T.I.D.
 Stop at 2,800/day

44. 44
Gabapentin – side effects
 Common:
 Somnolence
 Dizziness
 Ataxia, nervousness & tremor
 Be aware of:
 Joint & diffused body pain
 Peripheral edema
 Tolerance?

45. 45
Pregabalin
 Beneficial in:
 PO pain
 Diabetic peripheral neuropathy
 PHN
 Fibromyalgia
 Recommended dose: 75-600mg/day
 Almost as popular as Tylenol among chronic pain
patients
 Mostly used in Quebec off-label

46. Cannabinoids
Anonymous cross-sectional survey of 209 Canadians with
chronic pain1:
35% reported using cannabis
15% reported using cannabis for pain relief
Mainly young people, post trauma/surgery
A wide range of amounts and frequency of cannabis use
Pain, sleep & mood were all subjectively improved
1Ware MA et al, Pain 102;211-6:2003

47. 47
Cannabinoids
 Oral synthetic preparations:
 Nabilone (Cesamet): 0.5-4mg/day
 Dronabinol (Marinol): 2.5-10mg/day
 Sativex: cannabis-based buccal spray (neuropathic
pain)
Indications: - 2nd line adjuvant pain therapy
- Insomnia


48. 48
Chronic pain palliation –
Does it work?
Switching from pathogenetic treatment with alpha-lipoic
acid to gabapentin and other analgesics in
painful diabetic neuropathy: a real-world study in
outpatients1
1Ruessmann HJ et al, J Diabetes Complications 23;174:2009

49. 49
 443 chronic DM patients treated with lipoic acid
(600mg/d) for a mean period of 5 years
 Switched to gabapentin (600-2400mg/d) or D/C
therapy
 In the untreated group 73% developed pain within 2
weeks
 In the gabapentin group:
 45% developed side effects and stopped treatment
 55% of patients tolerating gabapentin did not
respond to a dose of 2400mg/g

50. Investments in pain palliation1
1Chappell AS, et al, Pain 146;253-60:2009

51. 1Bansal D et al, Diabetic Medicine 26;1019-26:2009

52. Outcome of chronic pain therapy
 4-year community study1:
 Increased prevalence (45.5 to 53.8%)
 79% still reported pain after 4 years
 Retrospective study of patients with CRPS2:
 None had recovered
 In most- only modest symptom improvement
 Improvement not necessarily associated with
therapy
1Elliott AM et al, Pain 99;299-307:2002; 2Schwartzman RJ et al, Clin J Pain 25;273-
80:2009

53. 53
Limitations of injection therapy
for LBP
 LBP will be experienced by most humans during
their life
 1/5 will consult her/his GP
 Specific diagnosis is lacking in ~ 85%
 The scientific evidence for many of the
interventions is lacking

54. 54
Outcome of injection therapy
Epidural steroids injection:
 Short term relief: NNT of 7
 Long term relief: NNT of 13
 The best study to date – no short or long-term
effect

55. 55
Outcome of injection therapy
Facet joint injections:
 Not effective
Trigger point injections:
 Hardly effective

56. Multiple reviews of injection outcome in
patients with LBP lasting for more than 1
month:
Treatment with facet, epidural or local
injections was not beneficial immediately
or late after the intervention
56

57. Summary – therapies for chronic pain
 The prognosis of chronic pain is frequently poor
despite advanced knowledge and novel therapeutic
tools
 Most resources are invested in palliation and not
prevention
 We, therefore, could focus more on:
57
 Prevention
 The environment
 Complementary & alternative medicine (CAM)

58. A call for change – prevention
rather than palliation
 Learn from other major diseases like cancer:
 1971: President Nixon declares ‘War on Cancer’1
 Cancer Act approved by Congress
 Massive funding of cancer therapy but not cancer
prevention
 Cancer mortality has not decreased as expected
(10% in 2005, lower than the expected 50%)
1Sporn MB, Lancet 347;1377–81:1996

59. The cancer model – palliation vs.
prevention
 While treatment is effective for certain cancers, it
ranks behind both early detection and risk-factor
modification in its potential to reduce cancer
mortality1
 Calls to view cancer not only as a curable illness but
primarily a preventable one2
1Danaei G et al, Lancet 366;1784 –93:2005; 2Bailar JC 3rd et al, N Engl J Med
336;1569–74 :1997

60. Preventing CNCP
Identify patients
at risk
Environmental
contribution
Preventive analgesia;
Multimodal analgesia; Immunization;
Other, yet to be found measures
Prevention of CNCP

61. Identifying high risk patients
 The selective tendency to develop CNCP is
still poorly understood
 The concept of “high risk pain patient”
should be recognized similar to high risk
cardiac or pulmonary patients
 Probably depends on genetic and phenotypic
characteristics

62. Genetic markers for CNCP
 The tendency to develop chronic pain in rats is 30-
70% genetic1
 Strong indications in humans:
 Haplotypes of the gene encoding catecholamine-O-methyltransferase
(COMT) could distinguish between
patients that will have low, moderate or high experimental
pain levels2
1Mogil JS, et al., Pain 80;67:1999; 2Diatchenko L, et al., Hum Mol Genet 14;135:2005

63. Phenotypic markers
 Previous exposure to painful stimuli
 Early life adversities
 Basic sensitivity to painful stimuli1
1Granot M, et al., Anesthesiology 98;1422:2003

64. The environment
Social conditions:
 Living in a socially compromised housing area
was significantly associated with increased
chronic musculoskeletal pain1
1Bergman-S, et al., J Rheumatol 28;1368:2001

65. The weather

66. The food we eat

67.  Supplementing rats with soy protein-rich diet
before, but not after surgical nerve injury prevents
the development of chronic neuropathic pain-like
syndrome1
1Shir Y, et al., Anesthesiology 95;1238:2001

68. Practical approach to prevent
some types of CNCP?
 Be familiar with possible predictors (personal &
family history, cultural, ethnical & social
background, psychological risk factors)
 Categorize level of risk
 Consider suitable preemptive (preventive) therapy
 Listen to your patients

69. 69
Immunization against
(neuropathic) pain?
 A study done in the USA1:
 In almost 40,000 older adults
 Early herpes zoster vaccination resulted in:
 Reduced incidence of acute shingles (51%)
 Reduced incidence of chronic shingles pain
(66%)
1Oxman MN et al. N Engl J Med 352;2271-84:2005

70. Post herpetic neuralgia
• 1 million new cases/year in the USA
• 15% will develop PHN
• In patients > 70 years old the chances for PHN are
up to 70% (52)
• Refractory to most common therapies

71. Controlling the brain
Following training humans can control activation
of specific brain regions involved with
nociception, resulting in significant pain relief1
1deCharms RC, et al, Proc Natl Acad Sci U S A 102;18626-31:2005

72. When to refer patients with CNCP to a
72
pain specialist?
 Uncontrolled pain
 Significant disability
 A comorbid psychiatric disorder
 Diagnostic evaluation for unknown etiology
 Consultation for treatment recommendations
 Need for treatment modalities that the PCP cannot
provide

73. Thank you
73